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RSC Advances
Page 16 of 22
DOI: 10.1039/C6RA15118C
ARTICLE
Journal Name
127.52, 126.47, 125.59, 123.50, 118.88. HRMS (TOF-ESI) Calcd pressure using rotary evaporator to obtain the product. The
for C17H13ClFN3O5, 265.270 (M)+; observed: 266.1729 (M+H)+.
product was finally dried to get the pure product.
Physical data of unknown compound of series 2 is given below: Yield: 90%; Red solid; IR (KBr, cm-1): 3196 (NH stretch), 1539
1
Synthesis of 2-bromo-N-(2-bromo-3-chloro-4-fluorophenyl)- (NO2 stretch), 857 (C-Cl stretch); H NMR (CDCl3, 400 MHz) δ:
6,7-dimethoxy-3-nitroquinolin-4-amine (2a).
10.28 (D2O exchangeable NH, s), 10.12 (D2O exchangeable NH,
100 mg of 1c was dissolved in 1 ml of THF. Then NBS (1 equiv) s), 7.71 (1H, d, J = 8 Hz), 7.60-7.69 (1H, m), 7.52 (1 H, d, J = 4
was added to the solution and refluxed for 24 h. Reaction was Hz), 7.47 (1H, d, J= 4 Hz), 7.29-7.32 (1H, dd, J12= 2.4, J13 =8 Hz),
monitored via TLC. The precipitates were washed with 7.25 (3H, m), 7.08- 7.12 (2H, m), 7.01-7.08 (1H, m), 6.68 (1H, d,
isopropyl alcohol followed by ether. The product was purified J = 8 Hz). Anal. Found. C, 51.09; H, 2.50; N, 11.39. Calcd for
via flash chromatography.
C21H12Cl4N4O2: C, 51.04; H, 2.45; N, 11.34.
Brown solid; yield 70%; mp: 257 °C; IR (KBr cm-1): 2921 (C-H Synthesis
stretch), 1495 (C=N Stretch), 1580 (C=C aromatic), 1219 (C-O diamine (15)
of
N4-benzyl-2-(3-chlorophenyl)quinoline-3,4-
stretch). 1H NMR (400 MHz, CDCl3, TMS = 0), 10.89 (D2O To a suspension of N-benzyl-2-chloro-3-nitroquinolin-4-amine
exchangeable NH, s), 8.40 (1H, s), 7.42 (1H, s), 7.19 (2H, s),
3.96 (3H, s), 3.90 (3H, s). Anal. Found. C, 38.21; H, 2.41; N, (2 equiv.) and the mixture was refluxed for 1 h. After the
7.83. Calcd for C17H11Br2ClFN3O4: C, 38.13; H, 2.07; N, 7.85; completion of the reaction (TLC), methanol was evaporated,
(2b) (250 mg, 1 mmol,) in methanol (1 mL) was added Sn/HCl
Synthesis of 3-Nitroquinoline-2,4-diol (13): 13 was compound was dried and purified through triturating with
synthesized using protocol reported in the literature.17 Mp: EtOAc and hexane mixture.
210-212 °C; IR (KBr, cm-1): 3313 (OH stretch), 2850 (C-C Yield: 30%; Brown solid; mp: 172 – 174°C; 1H NMR (CDCl3, 400
stretch), 2350 (C=N stretch), 1522 (NO2 stretch); 1H NMR MHz, δ with TMS = 0): 7.81 (1H, d, J = 8 Hz), 7.56 (1H, d, J = 8
(CDCl3, 400 MHz, δ with TMS = 0): 12.00 (1H, s), 8.05-8.03 (1H, Hz),7.46- 7.48 (1H, m), 7.37-7.39 (5H, m), 6.94-6.91 (1H, m),
dd, J12 = 1.2 Hz; J13 = 8.4 Hz), 7.62-7.58 (1H, m), 7.35-7.33 (1H, 5.02 (1H, D2O exchangeable NH, s), 4.60 (2H, D2O
d, J = 8 Hz), 7.26-7.22 (1H, m); 13C NMR (CDCl3, 100 MHz, δ exchangeable NH, s), 3.42 (2H, s). Anal. Found. C, 67.79; H,
with TMS = 0) δ: 157.11, 155.78, 138.21, 132.98, 126.41, 4.94; N, 14.88. Calcd for C16H14ClN3: C, 67.72; H, 4.97; N, 14.81.
124.41, 122.06, 115.76, 113.77; MS (ESI): m/z = 207.1 [M+1] +.
General Procedure for the synthesis of C-2 substituted
Synthesis of 2,4-dichloro-3-nitroquinoline (14): 14 was quinolines
synthesized using protocol reported in the literature.17 Mp: 94- 2-chloro-3-aminoquinoline (100 mg, 1 mmol), substituted-
96 °C; IR (KBr, cm-1): 1614 (C=N), 1490 (C=C), 1215 (C-N), 748 arylboronic acid (1.2 mmol), and palladium acetate (0.02
(C-Cl); 1H NMR (CDCl3, 400 MHz, δ with TMS = 0): 8.28-8.26 mmol) were taken in water and stirred at room temperature
(1H, dd, J12 = 1.2 Hz; J13 = 8.8 Hz), 8.13-8.10 (1H, d, J = 8.4 Hz), under inert conditions (TLC). The reaction mixture was
7.97-7.92 (1H, m), 7.83-7.79 (1H, m). 13C NMR (CDCl3, 100 extracted with ethyl acetate (10 x 3 mL). Product was purified
MHz, δ with TMS = 0) δ: 147.3, 144.78, 141.3, 132.19, 129.6, by column chromatography.
128.6, 125.5, 124.4.
Physical data of unknown compounds of series 4 is given
below:
Synthesis of 2-chloro-3-nitroquinolin-4-amine (2l) :
To a reaction vial, a suspension of 14 (240 mg, 1 mmol,) in Synthesis
methanol (1 mL) was added aq. ammonia (2 equiv.) and the diamine (4a)
of
N4-benzyl-2-(3-chlorophenyl)quinoline-3,4-
mixture was stirred for 6 h. After the completion of the Light Yellow semi-solid; yield 47%; IR (KBr, cm-1): 3200 (N-H
reaction the product was extracted with ethyl acetate, stretch), 1639 (C=N Stretch), 1544 (C=C aromatic), 550 (C-Cl
evaporated and dried. The product was purified via flash stretch).1H NMR (CDCl3, 400 MHz) δ: 8.12-8.09 (3H, m), 7.63-
chromatography.
7.61 (2H, m), 7.50-7.48 (4H, m), 7.08 (1H, t, J13= 16), 6.83 (1H,
1
Yield: 90%; Brown solid; mp: 132 – 134°C; H NMR (CDCl3, 400 d, J=12 Hz), 6.78 (1H, t, J13=4 Hz), 6.66-6.64 (1H, dd, J12=.5.76
MHz, δ with TMS = 0): 7.94 (1H, dd, J12 = 4 Hz; J13 = 8 Hz), 7.70 Hz), 5.23 (4H, NH2, CH2). Anal. Found. C, 73.49; H, 5.06; N,
(1H, dd, J12 = 4 Hz; J13 = 8 Hz), 7.49 (1H, d, J = 8 Hz), 7.20 (1H, d, 11.72. Calcd for C22H18ClN3: C, 73.43; H, 5.04; N, 11.68.
J = 12 Hz). Anal. Found. C, 48.38; H, 2.75; N, 18.83. Calcd for Synthesis of 1-(4-(3,4-diaminoquinolin-2-yl)phenyl)ethan-1-
C17H13ClFN3O5: C, 48.34; H, 2.70; N, 18.79.
one (4b)
Physical data of unknown compound of series 3 is given below: Light Yellow semi-solid; yield 52%; IR (KBr, cm-1): 3200 (NH2
Synthesis of N2,N4-bis(2,5-dichlorophenyl)-3-nitroquinoline- stretch), 1670 (C=O stretch), 1599 (C=N Stretch), 1547. 1H NMR
2,4-diamine (3l)
(CDCl3, 400 MHz) δ: 7.99 (2H, d, J = 4 Hz), 7.70 (1H, d, J = 4 Hz),
To a solution of 2,4-dichloro-3-nitroquinoline (100 mg, 0.41 7.52 (2H, d, J = 4 Hz), 7.21-7.18 (3H, m), 5.29 (4H, s) 2.75 (3H,
mmol, 1 eq.) in water (2 mL) were added triethylamine (0.6 s). HRMS (TOF-ESI) Calcd for C17H15N3O, 277.12 (M)+; observed:
mL, 0.49 mmol, 1.2 eq.) and 2,4-dichlorobenzylamine (0.7 mL , 278.2189 (M+H)+.
0.82 mmol, 2 eq.). The reaction mixture was stirred for 20 min Physical data of unknown compounds 5a, 5b, 16 and 17 are
in biotage microwave synthesizer. After the completion of the given below:
reaction (TLC), solid product was extracted with ethyl acetate Synthesis of 2-(naphthalen-2-yl)quinolin-3-amine (5a)
(10 mL × 3). Organics were washed with brine (10 mL × 3), Light Yellow semi-solid; yield 67%; IR (KBr, cm-1): 1600-1660
dried over anhydrous Na2SO4 and evaporated under reduced (napthyl ring), 1250 (C-N stretch), 2982 (C-H stretch), 1547
(C=C aromatic).1H NMR (CDCl3, 400 MHz) δ: 8.25 (1H, s), 8.06
16 | J. Name., 2012, 00, 1-3
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